Traumatic brain injury (TBI) involves two general phases of damage, the primary insult and secondary damage which can be targeted with resuscitative approaches. Two important disturbances early after injury, hypoperfusion and BBB permeability, are suggested to play key roles n the development of secondary damage. The objectives of this project are: (I) quantitative MRI assessment of contusion volume, cerebral blood flow (CBF), and blood-brain barrier (BBB) permeability in the controlled cortical impact (CCI) model of TBI in rats, (ii) MRI paradigm development of the acute assessment of pathophysiological outcome after CCI, (iii) assessment of novel therapies in severe TBI of both MRI and functional outcome methods in the CCI model, (iv) application of successful MRI paradigms to other TBI models, and (v) development of novel MRI methods to assess CCI. CBF measured by MRI using arterial spin tagging in a CCI model show reductions in injured cortex and hippocampus at 2.S to 3.5 h after TBI, and the results are in good agreement with those obtained with autoradiography studies. MRI measured a 85% reduction in CBF in the ipsilateral medial cortical segment (versus normal), in good agreement with the 78% CBF reduction (versus control ipsilateral) quantified within the contusion by autoradiography. A 1 year after injury, CBF is reduced in structures within and directly adjacent to the lesions, including injured cortex and hippocampus. CBF was not reduced in sites remote from the contusion in the injured hemisphere or in any structure in the contralateral hemisphere. Pilot MRI therapeutic tests involving augmentation of adenosine level in adult rats are currently being carried out. We are also investigating perfusion changes in a diffuse model of TBI in the immature. We will apply novel MRI methods to our CCI model as they become available. :